The overall objectives of the total project are to characterize the changes in reproductive hormone secretion and in hormone receptor activity in aging female rats, and to determine the functional capacity of the hypothalamic-pituitary-ovarian system as influenced by altered steroid hormone secretion during different reproductive states. The final goal of these studies will be to identify possible hormonal mechanisms by which the ovaries, pituitary and/or hypothalamus is (are) involved in the progressive cessation of regular ovulatory function in aging rats. Studies from our first year of project have revealed the functional significance of ovarian steroids on the neuroendocrine system, suggested that an excessive exposure to high circulating estrogens may cause an inhibition of postive feedback of LH secretion, and indicated that a deficiency of LH (or gonadotropin) secretion in aging rats may be directly related to the anovulatory function. These findings have provided direct evidence that a prolonged exposure to high circulating estrogens may inhibit the neuroendocrine mechanism of positive feedback of LH secretion. This may provide some insights into the mechanisms of amenorrhea or irregular menstrual function in women. Based on the findings from our first year project, the following studies are proposed for the coming year: To study the mechanisms by which a chronic elevation of circulating estrogens inhibits the positive feedback of LH secretion. Are changes in hypothalamic binding (uptake) of estradiol and/or hypothalamic catecholamine metabolism involved? To determine whether a progressive loss of positive feedback of LH secretion occurs in aging rats displaying irregular ovulatory cycles.